The reinforcing effects of amphetamine (AMPH)-like psychostimulants are mediated through the dopamine (DA) transporter (DAT). Recent in vitro data suggest insulin can modulate the DA system by promoting DAT cell surface expression, which would modify the cellular and behavioral effects of AMPH. Thus, brain insulin systems represent a novel and currently unresolved therapeutic target for psychostimulant abuse. To investigate the role of insulin in the regulation of DA signaling in vivo, the current proposal seeks to use blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI), high-speed chronoamperometry and synaptosomal DA uptake studies to evaluate the functionality of DA systems within insulin-depleted animals in response to both acute and chronic psychostimulant exposure. These studies will utilize the streptozotocin model of hypoinsulinemia in rodents and implement various pharmacological tools to assess the role of insulin signaling in the regulation of DAT function. Through combining these innovative approaches with well-established methodologies, this effort will help clarify an emerging role for insulin in the pharmacology of psychostimulants, which is vital to addressing their abuse. [unreadable] [unreadable]